The goal of this investigation is to develop an efficient method for the large scale purification of human fibroblastoid interferon to homogeneity in order to produce sufficient purified human interferon (batches of 100-200 micrograms of pure interferon) for its structural/functional analysis. The availability of large amounts of purified interferon will make it possible to determine whether the anti-tumor and cell multiplication inhibitory effect of human interferon is due to interferon itself. The key programs to be included in this proposal are listed below: (1) The production of 1 X 10 to the 10th power reference units of human fibroblastoid interferon per annum for its purification. (2) The preparation of a highly purified interferon by a modified method of Berthold, Tan and Tan (1978) for immunization. (3) The purification of human interferon by antibody-affinity column chromatography and by polyacrylamide gel electrophoresis. (4) Chemical analysis and chemical modifications of the purified interferon. (5) Preparation of a spectrum of biologically active radioactively-labelled interferons to be used as specific molecular probes. (6) Biological analysis of the purified interferon derived from (2) and (3), and of the chemically modified interferons derived from (4) and (5).